Intravascular coagulation is preceded by the formation of soluble complexes of fibrin in blood. The proposed studies are directed to 1) refine and simplify methods of analysis of the complexes, 2) establish by electron microscopy the mechanism of cellular uptake and metabolism of the complexes, and 3) assess the role of fibrinopeptide B in both aggregation and metabolism of fibrin. Newly invented systems for zonally immobilizing proteins in profile of their properties are proposed to provide means for rapid and precise characterization of the molecular weight distribution and interactive properties of fibrin complexes and other altered forms of fibrinogen in blood. These systems employ glyoxal agarose as a medium which can be used to separate variant forms of proteins by either chromatography or electrophoresis, and to fix them in place for analysis of their biochemical reactivities in relation to their physical properties. Pilot studies indicate that zonal immobilization systems provide simple and inexpensive alternatives to existing methods of analysis of fibrin complexes, and further suggest that subclassifications made possible with them will provide new criteria for assessment of intravascular coagulation. Visualization of the routes of transport and uptake of fibrinogen and fibrin in cells and vascular tissue has been made possible by development of a non-destructive means of labelling the molecules with hemepeptide for electron-dense staining. Further, it will be possible to study the transport and binding in relation to the degree of aggregation of the molecules. Specific removal of fibrinopeptide B by copperhead venom has been shown to yield a form of fibrin which shares many properties of regular fibrin but is dissociable into monomers on dilution. This dissociability provides means for assessing the relative importance of aggregation and specific receptor interactions in cellular uptake of fibrin.